AME

Question 2

Aldosterone selective tissues: (4)

Answer 2

distal tubulesweat glandssalivary glandscolon

Question 3

Oxidation of cortisol to 11-dehydrocortisol (or cortisone) greatly reducesactivity at the mineralocorticoid receptor. This is catalysed by ______

Answer 3

11β-hydroxysteroid dehydrogenase (11βHSD2) Type 2”Target Cell Guardian of the MR”11βHSD Type 2 can oxidise glucocorticoids Especially active in kidney (collecting ducts), colon, salivary glands and placenta

Question 4

Mutations in 11βHSD gene Coding sequence (loss of function) Regulatory region (decreased expression) Enzyme inhibition e.g. glycyrrhetinic acid in ___

Answer 4

liquorice

Question 5

Defective gene : homozygous recessiveAME usually confined to consanguinous • BUT ____might have increased ability to conserve sodium under conditions of sodium deprivation –>selective advantage –> conserved mutations.

Answer 5

heterozygotes

Question 6

Inhibition of 11βHSD 2 by: ________ (e.g. deoxycholate) ________(e.g. progesterone) ________ (e.g. cholesterol, lanosterol)Endogenous mammalian compounds Carbenoxolone (GA ester) FurosemideIatrogenic• Glycyrrhetinic acid (e.g. in liquorice, herbal remedies)

Answer 6

1. Bile pigments2. Steroids 3. Sterols

Question 7

Clinical Symptoms of AME: (5)

Answer 7

 Anti-natriuresis Hypervolemic hypertension Increased fluid resorption Kaliuresis leading to hypokalemia Muscle weakness (including cardiac), fatigue

Question 8

Placental 11βHSD protects fetusCortisol—-> ______If placental 11βHSD fails: Increased passage of cortisol to fetus Prevents further growth of tissues Stimulates premature differentiation offetal tissues Culminates in ______

Answer 8

1. Cortisone2. IUGR

Question 9

11βHSD Type __ can re-activate glucocorticoids for actions at the MROverexpression, especially in fat, can –> to symptoms similar to “_____” and apparent glucocorticoid excess cortisone—> cortisol 11-Dehydro-corticosterone–>corticosterone

Answer 9

1. 12. Metabolic syndrome

Question 10

17βHSD can modulate steroid potencyAndrostenedione–>__________Estrone–>___________

Answer 10

1. testosterone2. estradiol

Question 11

What enzyme catalyzes:testosterone–> 5a-DHT

Answer 11

1. 5a-reductase

Question 12

Which enzymes?progesterone–> AllopregnanoloneAllopregnanolone cannot act at PR but is very potent at________

Answer 12

1. 5a reductase, 3aHSD2. GABA-A Receptors

Question 13

distinguish between Conn’s and AME?

Answer 13

Conn’s: adrenal tumour: aldosterone levels highAME: aldosterone low/normal

Question 14

Liddle’s syndrome (pseudoaldosteronism)autosomal ______early and frequent severe_____low____metabolic alkalosis due to low K+Normal/low _______caused by dysregulation in ENaC

Answer 14

1. dominant2. hypertension3. renin4. aldosterone Treatment : low sodium diet and a K+ sparing diuretic that directly blocks the sodium channel. amiloride and triamterene; spironolactone ineffective –> regulates aldosterone, Liddle’s does not respond to this regulation.